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Abstract
Background: Valproic acid (VPA)andcarbamazepine (CBZ),twowidely used antiepileptic drugs, have recentlybeenfound to inhibit histone deacetylases (HDAC). HDAC inhibitors (HDACIs) have various effects on cancer cells.
Objectives: The aim of this study was to compare the anticancer activity of these drugs on SW480 colon cancer cell lines.
Methods: In the present experimental study, implemented during 2014 - 2015 in Iran, after incubation of cells into 96-well plates with 5,500 cells/well, the tested drugs were added, and cytotoxic effects were assessed by MTT. Moreover, after incubation of 8106 cells in 75 cm2 flasks to obtain-catenin levels and 106 cells in a six-well plate to obtain vascular endothelial growth factor (VEGF) levels , these levels were estimated using enzyme-linked immunosorbent assay (ELISA) analysis.
Results: Through MTT assay, we found that the inhibitory concentration of 50% (IC50) values for VPA and CBZ were 2.5 mM and 5 M, respectively in comparison to controls in terms of total concentration and times evaluated (P < 0.0001). We also found that treatments with these drugs decreased levels of-catenin (P < 0.0001) and VEGF (P < 0.0001) significantly more than controls.
Conclusions: VPA and CBZ treatments caused a decrease i-Catenin and VEGF levels in SW480 colon cancer cell lines. These results suggest that CBZ can be considered a potential antitumor drug with potencies different from VPA.
Keywords: Histone Deacetylase Inhibitor,-Catenin, VEGF
1. Background
Valproic acid (VPA) is a broad spectrum antiepileptic drug that has also been used in the treatment of bipolar disorders, neuropathic pain, and migraine prophylaxis. However, the mechanisms of action for VPA are currently unknown. Its antiepileptic effects primarily depend on the increased gamma aminobutyric acid function and its interactions with sodium and calcium channels. The anticonvulsant drug carbamazepine (CBZ) isknownto have antimanic and prophylactic effects in the treatment of manic depressive disorders. CBZ blocks Na+ channels (1).
In the past few years, histone deacetylases inhibitors (HDACIs) have proven to be powerful inducers of cancer cell growth arrest (including in drug resistant subtypes), differentiation, and apoptotic cell death of transformed cells. They also inhibit angiogenesis and sensitize cancer cells to overcome drug resistance when used in combination with other anticancer agents. In addition, histone hyperacetylation has proven to be important in the carcinoma process, and HDACIs firmly bind...